Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1.
OBJECTIVE
Liver disease has been described in 10%-15% of patients with autoimmune polyglandular syndrome type 1 (APS-1). After the discovery of cytochrome P450 1A2 (CYP1A2) as a hepatocellular autoantigen in liver-kidney microsomal autoantibody (LKM)-positive patients with APS-1, the investigation of antiliver antibodies was extended to 11 Sardinian patients with APS-1.


METHODS
Indirect immunofluorescence and Western blotting analysis were performed to study the antiliver antibodies.


RESULTS
Immunofluorescence revealed LKM antibodies in 3 patients with APS-1, 1 of whom died of fulminant hepatitis. Western blotting showed a liver microsomal protein band of approximately 51 kilodaltons in the LKM-positive sera of these 3 patients. Western blotting performed with recombinant cytochrome P450 enzymes allowed the identification of CYP2A6 as a specific target antigen.


CONCLUSIONS
LKM antibodies in APS-1 sera are specifically directed against CYP1A2 or CYP2A6, but their diagnostic and prognostic significance for liver disease remain to be determined.
Clemente
M G
MG
Istituto di Clinica e Biologia dell'età evolutiva, Università degli Studi di Cagliari, Italy.
Meloni
A
A
Obermayer-Straub
P
P
Frau
F
F
Manns
M P
MP
De Virgiliis
S
S
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001324:Autoantigens / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D019388:Cytochrome P-450 CYP1A2 / Q000032:analysis* / Q000276:immunology; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis* / Q000276:immunology; D010375:Pedigree; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; C060729:anti-liver kidney microsome antibody; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D019388:Cytochrome P-450 CYP1A2; D065637:Cytochrome P-450 CYP2A6